A unified genetic theory for sporadic and inherited autism
A unified genetic theory for sporadic and inherited autism
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DOI：
10.1073/pnas.0705803104
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发表时间：
2007-07-31
影响因子：
11.1
通讯作者：
Wigler, Michael
中科院分区：
文献类型：
--
作者：
Zhao, Xiaoyue;Leotta, Anthony;Wigler, Michael
自闭症是所有认知发育障碍中最明显由基因决定的疾病之一，男性比女性更容易受到影响。我们分析了来自自闭症遗传资源交换（AGRE）的多重家庭的自闭症风险，并找到了显性遗传给男性后代的有力证据。通过结合普遍接受的自闭症和兄弟姐妹复发率，我们发现一个简单的遗传模型非常适合，在该模型中，大多数家庭分为两种类型：少数家庭的男性后代患自闭症的风险接近 50%，而绝大多数家庭的男性后代患自闭症的风险较低。我们提出了一种将这两类家庭联系起来的解释：低风险家庭中的散发性自闭症主要是由自发突变引起的，男性外显率较高，女性外显率相对较差；高风险家庭来自那些携带新的致病突变但不受影响并反过来以显性方式将突变遗传给后代的后代（通常是女性）。
Autism is among the most clearly genetically determined of all cognitive-developmental disorders, with males affected more often than females. We have analyzed autism risk in multiplex families from the Autism Genetic Resource Exchange (AGRE) and find strong evidence for dominant transmission to male offspring. By incorporating generally accepted rates of autism and sibling recurrence, we find good fit for a simple genetic model in which most families fall into two types: a small minority for whom the risk of autism in male offspring is near 50%, and the vast majority for whom male offspring have a low risk. We propose an explanation that links these two types of families: sporadic autism in the low-risk families is mainly caused by spontaneous mutation with high penetrance in males and relatively poor penetrance in females; and high-risk families are from those offspring, most often females, who carry a new causative mutation but are unaffected and in turn transmit the mutation in dominant fashion to their offspring.